Postoperative Capecitabine with Concurrent Intensity-Modulated Radiotherapy or Three-Dimensional Conformal Radiotherapy for Patients with Stage II and III Rectal Cancer

Background

The aim of this study was to evaluate the survival outcomes and toxicity of postoperative chemoradiotherapy with capecitabine and concurrent intensity-modulated radiotherapy (IMRT) or three-dimensional conformal radiotherapy (3D-CRT) in patients with stage II and III rectal cancer.

Patients

We recruited 184 patients with pathologically proven, stage II or III rectal cancer. Following total mesorectal excision (TME), the patients were treated with capecitabine and concurrent IMRT/3D-CRT. The treatment regimen consisted of two cycles of oral capecitabine (1600 mg/m²/day), administered twice daily from day 1–14 of radiotherapy, followed by a 7-day rest. The median pelvic dose was 50 Gy in 25 fractions. Oxaliplatin-based adjuvant chemotherapy was administered after the chemoradiotherapy.

Results

The 5-year overall survival, disease-free survival and locoregional control (LRC) rates were 85.1%, 80% and 95.4%, respectively. Grade 3 and 4 toxicities were observed in 28.3% of patients during treatment. Grade 3 or 4 late toxicity, including neurotoxicity or gastrointestinal toxicity, was only observed in nine patients (4.9%).

Conclusions

This study demonstrated that capecitabine chemotherapy with concurrent IMRT/3D-CRT following TME is safe, is well tolerated and achieves superior LRC and favorable survival rates, with acceptable toxicity.     

Understanding Sexual Activity and Chlamydia Testing Rate Based on Linked National Survey and Medicaid Claims Data

Background

Monitoring adherence to national recommendations for annual chlamydia screening of female adolescents and young adult women is important for targeting quality improvement interventions to improve low screening rates. However, accurate measurement of rates may vary depending on the data source used to determine eligible sexually-active women.

Methods

The 2001–2004 NHANES data linked with Medicaid administrative data by respondent’s unique identifier, the 2011–2012 NHANES data, and the 2004 and 2010 Medicaid data were used in this cross-sectional analysis. We defined self-reported sexual activity by self-reported sexual behaviors, claim-identified sexual activity by reproductive-related claims among women who had ≥ one healthcare claim, HEDIS-defined sexual activity by reproductive-related claims among women who were enrolled in Medicaid for ≥330 days and had ≥ one healthcare claim, and chlamydia tests by claims submitted in the 12 months prior to the survey interview.

Results

Of Medicaid women aged 18–25 years, 91.5% self-reported to be sexually-active. Of self-reported sexually-active women aged 18–25 years, 92.0% had ≥ one healthcare claim in the 12 months prior to the survey interview; of this subpopulation, only 58.8% were enrolled in Medicaid for ≥ 330 days in the 12 months prior to the survey interview; of this further subpopulation, 74.1% had healthcare claims identifying them as sexually-active in the 12 months prior to the survey interview. Of HEDIS-defined sexually-active women, 42.4% had chlamydia testing.

Conclusion

Our study suggests that the number of sexually-active women aged 18–25 years used as the denominator in the chlamydia testing measure could be significantly different, depending upon the definition applied and the data used. Our data highlight the limited representativeness of Medicaid population in the current HEDIS measure on chlamydia testing when a high proportion of women who were enrolled in Medicaid for <330 days had been excluded from the measure. The interventions that can improve the proportion of women who were enrolled in Medicaid for ≥ 330 days among all young Medicaid women are needed not only for improving health care services, but also for measuring quality of healthcare.     

Determination of Zygosity in Adult Chinese Twins Using the 450K Methylation Array versus Questionnaire Data

Previous studies have shown that both single nucleotide polymorphisms (SNPs) and questionnaires-based method can be used for twin zygosity determination, but few validation studies have been conducted using Chinese populations. In the current study, we recruited 192 same sex Chinese adult twin pairs to evaluate the validity of using genetic markers-based method and questionnaire-based method in zygosity determination. We considered the relatedness analysis based on more than 0.6 million SNPs genotyping as the golden standards for zygosity determination. After quality control, qualified twins were left for relatedness analysis based on identical by descent calculation. Then those same sex twin pairs were included in the zygosity questionnaire validation analysis. Logistic regression model was applied to assess the discriminant ability of age, sex and the three questions in zygosity determination. Leave one out cross-validation was used as a measurement of internal validation. The results of zygosity determination based on 65 SNPs in 450k methylation array were all consistent with genotyping. Age, gender, questions of appearance confused by strangers and previously perceived zygosity consisted of the most predictable model with a consistency rate of 0.8698, cross validation predictive error of 0.1347. For twin studies with genotyping and\or 450k methylation array, there would be no need to conduct other zygosity testing for the sake of costs consideration.     

PFTK1 Promotes Gastric Cancer Progression by Regulating Proliferation,Migration and Invasion

PFTK1, also known as PFTAIRE1, CDK14, is a novel member of Cdc2-related serine/threonine protein kinases. Recent studies show that PFTK1 is highly expressed in several malignant tumors such as hepatocellular carcinoma, esophageal cancer, breast cancer, and involved in regulation of cell cycle, tumors proliferation, migration, and invasion that further influence the prognosis of tumors. However, the expression and physiological significance of PFTK1 in gastric cancer remain unclear. In this study, we analyzed the expression and clinical significance of PFTK1 by Western blot in 8 paired fresh gastric cancer tissues, nontumorous gastric mucosal tissues and immunohistochemistry on 161 paraffinembedded slices. High PFTK1 expression was correlated with the tumor grade, lymph node invasion as well as Ki-67. Through Cell Counting Kit (CCK)-8 assay, flow cytometry, colony formation, wound healing and transwell assays, the vitro studies demonstrated that PFTK1 overexpression promoted proliferation, migration and invasion of gastric cancer cells, while PFTK1 knockdown led to the opposite results. Our findings for the first time supported that PFTK1 might play an important role in the regulation of gastric cancer proliferation, migration and would provide a novel promising therapeutic strategy against human gastric cancer.     

cAMP/PKA Pathways and S56 Phosphorylation Are Involved in AA/PGE2-Induced Increases in rNaV1.4 Current

Arachidonic acid (AA) and its metabolites are important second messengers for ion channel modulation. The effects of extracellular application of AA and its non-metabolized analogue on muscle rNa_V1.4 Na⁺ current has been studied, but little is known about the effects of intracellular application of AA on this channel isoform. Here, we report that intracellular application of AA significantly augmented the rNa_V1.4 current peak without modulating the steady-state activation and inactivation properties of the rNa_V1.4 channel. These results differed from the effects of extracellular application of AA on rNa_V1.4 current. The effects of intracellular AA were mimicked by prostaglandin E₂ but not eicosatetraynoic acid (ETYA), the non-metabolized analogue of AA, and were eliminated by treatment with cyclooxygenase inhibitors, flufenamic acid, or indomethacin. AA/PGE₂-induced activation of rNa_V1.4 channels was mimicked by a cAMP analogue (db-cAMP) and eliminated by a PKA inhibitor, PKAi. Furthermore, inhibition of EP2 and EP4 (PGE₂ receptors) with AH6809 and AH23848 reduced the intracellular AA/PGE₂-induced increase of rNa_V1.4 current. Two mutated channels, rNa_V1.4S56A and rNa_V1.4T21A, were designed to investigate the role of predicted phosphorylation sites in the AA/PGE₂–mediated regulation of rNa_V1.4 currents. In rNa_V1.4S56A, the effects of intracellular db-cAMP, AA, and PGE₂ were significantly reduced. The results of the present study suggest that intracellular AA augments rNa_V1.4 current by PGE₂/EP receptor-mediated activation of the cAMP/PKA pathway, and that the S56 residue on the channel protein is important for this process.     

Flow‐injection chemiluminescence method to detect a β2 adrenergic agonist

A new method for the detection of β₂ adrenergic agonists was developed based on the chemiluminescence (CL) reaction of β₂ adrenergic agonist with potassium ferricyanide–luminol CL. The effect of β₂ adrenergic agonists including isoprenaline hydrochloride, salbutamol sulfate, terbutaline sulfate and ractopamine on the CL intensity of potassium ferricyanide–luminol was discovered. Detection of the β₂ adrenergic agonist was carried out in a flow system. Using uniform design experimentation, the influence factors of CL were optimized. The optimal experimental conditions were 1 mmol/L of potassium ferricyanide, 10 µmol/L of luminol, 1.2 mmol/L of sodium hydroxide, a flow speed of 2.6 mL/min and a distance of 1.2 cm from ‘Y₂’ to the flow cell. The linear ranges and limit of detection were 10–100 and 5 ng/mL for isoprenaline hydrochloride, 20–100 and 5 ng/mL for salbutamol sulfate, 8–200 and 1 ng/mL for terbutaline sulfate, 20–100 and 4 ng/mL for ractopamine, respectively. The proposed method allowed 200 injections/h with excellent repeatability and precision. It was successfully applied to the determination of three β₂ adrenergic agonists in commercial pharmaceutical formulations with recoveries in the range of 96.8–98.5%. The possible CL reaction mechanism of potassium ferricyanide–luminol–β₂ adrenergic agonist was discussed from the UV/vis spectra. Copyright © 2014 John Wiley & Sons, Ltd.     

Significance of tumour cell HLA‐G5/‐G6 isoform expression in discrimination for adenocarcinoma from squamous cell carcinoma in lung cancer patients

Human leucocyte antigen (HLA)‐G has seven isoforms, of which HLA‐G1‐G4 are membrane‐bound and HLA‐G5‐G7 are soluble. Previous studies reinforced HLA‐G expression was strongly related to poor prognosis in different types of cancers. Among these studies, the monoclonal antibody (mAb) 4H84 was used which detects all HLA‐G isoform heavy chain; unfortunately, leaves the specific types of isoforms expressed in lesions undistinguished and its clinical significance needs to be clarified. To explore clinical significance of lesion soluble HLA‐G (sHLA‐G) in non‐small‐cell lung cancer (NSCLC), mAb 5A6G7 recognizing HLA‐G5/‐G6 molecules was used. Tumour cell sHLA‐G expression in 131 primary NSCLC lesions (66 squamous cell carcinoma, 55 adenocarcinoma and 10 adenosquamous carcinoma) were analysed with immunohistochemistry. Data showed that sHLA‐G expression was observed in 34.0% (45/131) of the NSCLC lesions, which was unrelated to patient age, sex, lymph nodal status, tumour–node–metastasis stage and patient survival. However, tumour cell sHLA‐G expression in lesions was predominately observed in adenocarcinoma lesions (73.0%, 40/55) which was significantly higher than that in squamous cell carcinoma (6.0%, 4/66) and adenosquamous carcinoma lesions (10.0%, 1/10, P < 0.001). The area under the receiver operating characteristic curve for lesion sHLA‐G was 0.833 (95% CI: 0.754–0.912, P < 0.001) for adenocarcinoma versus squamous cell carcinoma. Our findings for the first time showed that tumour cell sHLA‐G was predominately expressed in lung adenocarcinoma, which could be a useful biomarker to discriminate adenocarcinoma from squamous cell carcinoma in NSCLC patients.